Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)

An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

The percentage of participants who died by Day 28 was calculated.

The percentage of participants who died by Week 8 was calculated.

The percentage of participants who died by Week 12 was calculated.

The percentage of participants who died by Week 24 was calculated.

The percentage of participants with survival at Day 28 using Kaplan-Meier was calculated.

The percentage of participants with survival at Week 8 using Kaplan-Meier was calculated.

The percentage of participants with survival at Week 12 using Kaplan-Meier was calculated.

The percentage of participants with survival at Week 24 using Kaplan-Meier was calculated.

The percentage of participants who received a liver transplant by week 24 was calculated.

The occurrence of HRS was confirmed based on the following diagnostic criteria from the International Ascites Club (IAC): 1) Cirrhosis with ascites, 2) Diagnosis of acute kidney injury (AKI) according to the ICA-AKI criteria, 3) Absence of shock, 4) No current or recent treatment with nephrotoxic drugs, and 5) Absence of parenchymal renal disease as indicated by proteinuria >500 mg/day, microhematuria (> 50 red blood cells per high power field) and/or abnormal renal ultrasonography.

The occurrence of bacterial, fungal, or viral infections was recorded. An infection was considered definite in participants with clinical evidence of infection and a positive culture from a normally sterile source (with the exception of spontaneous bacterial peritonitis).

Length of initial hospital stay from first dose date of study drug was calculated for participants who were released from initial hospitalization separately from those who died during their initial hospitalization.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

The Lille score is a tool used to predict which participants with severe alcoholic hepatitis (AH) were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille response was defined as having a Lille score < 0.45.

The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7. Lille null response was defined as having a Lille score ≥ 0.56.

The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). The Lille score was calculated using baseline factors: age, albumin, total bilirubin, serum creatinine, prothrombin time; and the change in total bilirubin between baseline (Day 1) and Day 7.

The Lille score is a tool used to predict which participants with severe AH were not responding to corticosteroid therapy. It ranges between 0 and 1, with low scores (< 0.16) indicating complete response or positive response to steroids (continue therapy) and high scores (≥ 0.56) indicating no response or poor response to steroids (stop therapy). MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. A scoring system combining the Lille score at Day 7 and the baseline MELD score was used to calculate the percentage of participants expected to die by Month 2 and by Month 6.

MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity. Change from Baseline was calculated as the value at endpoint minus the value at Baseline.

CPT scores are used to assess the severity of cirrhosis. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease

Baseline Maddrey DF score is a prognostic tool used to determine the next step of treatment based on the severity of AH. Maddrey DF score of < 32 indicates mild to moderate AH and a lower chance of death in the next few months. Maddrey DF score of ≥ 32 indicates severe AH and a higher chance of death in the next few months. The score has no bounds.